Summary
Most α2-adrenoceptor antagonists do not discriminate between pre- and postjunctional α2-adrenoceptors, and this has led to the commonly held belief that pre- and postjunctional α2-adrenoceptors may represent one homogeneous population of receptors. SK&F 104078 has been shown to be a potent antagonist at postjunctional α2-adrenoceptors at concentrations that do not block prejunctional α2-adrenoceptors. Thus, SK & F 104078 is a competitive postjunctional α2-adrenoceptor antagonist in canine and rabbit saphenous veins, canine saphenous artery and human platelet with a dissociation constant of approximately 100 nmol/l. Conversely, SK & F 104078 is inactive as a prejunctional α2-adrenoceptor antagonist in atria from dog, guinea pig, rabbit and rat, and in guinea-pig ileum at concentrations up to 10,000 nmol/l. Likewise, SK & F 104078 has the ability to block postjunctional arterial α2-adrenoceptors in vivo in the pithed rat at doses that do not inhibit prejunctional α2-adrenoceptors in the same model. The results suggest that pre- and postjunctional α2-adrenoceptors may not represent one homogeneous class, but rather are discrete subtypes of the α2-adrenoceptor that may be differentiated by SK & F 104078.
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References
Alabaster VA, Peters CJ (1984) Pre- and postjunctional α2-adrenoceptors can be differentially antagonized. Br J Pharmacol 81:163P
Arunlakshana O, Schild HO (1959) Some quantitative uses of drug antagonists. Br J Pharmacol 14:48–58
Berridge TR, Doxey JC, Roach AG, Strachan DA, Virdee NK (1984) Antagonist effects of idazoxan and yohimbine against several α2-adrenoceptor agonists in pithed rats. Br J Pharmacol 81:86P
de Jonge A, Santing PN, Timmermans PBMWM, van Zwieten PA (1981) A comparison of peripheral pre- and postsynaptic α2-adrenoceptors using meta-substituted imidazolidines. J Auton Pharmacol 1:377–383
DeMey J, Vanhoutte PM (1981) Uneven distribution of postjunctional α1- and α2-adrenoceptors in canine arterial and venous smooth muscle. Circ Res 48:875–884
Docherty JR, Hyland L (1985) No evidence for differences between pre- and postjunctional α2-adrenoceptors. Br J Pharmacol 86:335–339
Drew GM, Whiting SB (1979) Evidence for two distinct types of postsynaptic α-adrenoceptors in vascular smooth muscle in vivo. Br J Pharmacol 67:207–215
Hieble JP, Pendleton RG (1979) Effects of ring substitution on the pre- and postjunctional α-adrenergic activity of aryliminoimidazolidines. Naunyn-Schmiedeberg's Arch Pharmacol 309:217–224
Hieble JP, Roesler JM, Fowler PJ, Matthews WD, DeMarinis RM (1985) A new approach to antihypertensive therapy via blockade of the postjunctional alpha2-adrenoceptor. In: Bevan JA, Goldfraind T, Maxwell RA, Stoclet JC, Worcel M (eds) Vascular neuroeffector mechanisms. Elsevier, Amsterdam, pp 159–164
Langer SZ, Massingham R, Shepperson N (1980) Presence of postsynaptic α2-adrenoceptors of predominantly extrasynaptic location in the vascular smooth muscle in the dog hind limb. Clin Sci (Oxf) 59:225s-228s
Levitt B, Hieble JP (1985) Characterization of pre- and postjunctional alpha-adrenoceptors in rabbit lateral saphenous vein. Fed Proc 44:1465
Madjar H, Docherty JR, Starke K (1980) An examination of pre-and postsynaptic α-adrenoceptors in the autoperfused rabbit hindlimb. J Cardiovasc Pharmacol 2:619–627
McGrath JC, Flavahan NA, McKean CE (1982) α1- and α2-adrenoceptor mediated pressor and chronotropic effects in the rat and rabbit. J Cardiovasc Pharmacol 4:S101-S107
Medgett IC, Hicks PE, Langer SZ (1984) Smooth muscle α2-adrenoceptors mediate vasoconstrictor responses to exogenous norephinephrine and to sympathetic stimulation to a greater extent in spontaneously hypertensive than in Wistar Kyoto rat tail arteries. J Pharmacol Exp Ther 231:159–165
Ruffolo RR, Jr (1982) Important concepts of receptor theory. J Auton Pharmacol 2:277–295
Ruffolo RR Jr, Patil PN, Miller DD (1983) Adrenoceptor-mediated effects of optically active catecholimidazolines in pithed rat. Naunyn-Schmiedeberg's Arch Pharmacol 323:221–227
Ruffolo RR, Jr, Waddell JE (1982) Receptor interaction of imidazolines. IX. Cirazoline is an α1-adrenergic agonist and α2-adrenergic antagonist. J Pharmacol Exp Ther 222:29–36
Ruffolo RR, Jr, Zeid RL (1985) Relationship between α-adrenoceptor occupancy and responses for the α1-adrenoceptor agonist, cirazoline, and the α2-adrenoceptor agonist, B-HT 933, in canine saphenous vein. J Pharmacol Exp Ther 235:636–643
Sulpizio AC, Hieble JP (1987) Demonstration of α2-adrenoceptor mediated contraction in the isolated canine saphenous artery treated with BAY k 8644. Eur J Pharmacol 135:107–110
Timmermans PBMWM, Kwa HY, van Zwieten PA (1979) Possible subdivision of postsynaptic α-adrenoceptors mediating pressor responses in the pithed rat. Naunyn-Schmiedeberg's Arch Pharmacol 310:189–193
Waterfall JF, Rhodes KF, Lattimer N (1985) Studies of α2-adrenoceptor antagonist potency in vitro: comparisons in tissues from rats, rabbits, dogs and humans. Clin Sci 68 (Suppl 10): 21S-24S
Wilffert B, Timmermans PBMWM, van Zwieten PA (1982) Extrasynaptic location of α2- and noninnervated β2-adrenoceptors in the vascular system of the pithed normotensive rat. J Pharmacol Exp Ther 221:762–768
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Ruffolo, R.R., Sulpizio, A.C., Nichols, A.J. et al. Pharmacologic differentiation between pre- and postjunctional α2-adrenoceptors by SK & F 104078. Naunyn-Schmiedeberg's Arch Pharmacol 336, 415–418 (1987). https://doi.org/10.1007/BF00164875
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DOI: https://doi.org/10.1007/BF00164875